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Pre-immature dendritic cells (PIDC) pulsed with HPV16 E6 or E7 peptide are capable of eliciting specific immune response in patients with advanced cervical cancer

BACKGROUND: The protein products of the early genes E6 and E7 in high-risk HPV types 16 and 18 have been implicated in the oncogenic capability of these viruses. Therefore, these peptides represent attractive vaccine therapy targets. METHODS: Thirty-two patients with advanced cervical cancer (HPV16...

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Autores principales: Rahma, Osama E, Herrin, Vincent E, Ibrahim, Rami A, Toubaji, Anton, Bernstein, Sarah, Dakheel, Omar, Steinberg, Seth M, Eid, Rasha Abu, Mkrtichyan, Mikayel, Berzofsky, Jay A, Khleif, Samir N
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269078/
https://www.ncbi.nlm.nih.gov/pubmed/25510844
http://dx.doi.org/10.1186/s12967-014-0353-4
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author Rahma, Osama E
Herrin, Vincent E
Ibrahim, Rami A
Toubaji, Anton
Bernstein, Sarah
Dakheel, Omar
Steinberg, Seth M
Eid, Rasha Abu
Mkrtichyan, Mikayel
Berzofsky, Jay A
Khleif, Samir N
author_facet Rahma, Osama E
Herrin, Vincent E
Ibrahim, Rami A
Toubaji, Anton
Bernstein, Sarah
Dakheel, Omar
Steinberg, Seth M
Eid, Rasha Abu
Mkrtichyan, Mikayel
Berzofsky, Jay A
Khleif, Samir N
author_sort Rahma, Osama E
collection PubMed
description BACKGROUND: The protein products of the early genes E6 and E7 in high-risk HPV types 16 and 18 have been implicated in the oncogenic capability of these viruses. Therefore, these peptides represent attractive vaccine therapy targets. METHODS: Thirty-two patients with advanced cervical cancer (HPV16 or 18 positive) were treated with HPV16 E6 (18–26) (Arm A) or HPV16 E7 (12–20) peptide (Arm B) pulsed on PBMCs in order to illicit immune response against the relevant peptide on both arms. These PBMCs were cultured for a short time (48 hours only) and in the presence of GM- CSF, accordingly, they were identified as “Pre-Immature Dentritic Cells”. RESULTS: 51Cr release assay and ELISPOT demonstrated evidence of specific immune response against the relevant peptide in 10/16 (63%) evaluable patients in arm A and 7/12 (58%) in arm B. HPV16 E6 was found to be homologous to HPV18 E6 in both vivo and vitro. The median overall survival (OS) and progression free survival (PFS) for the full cohort was 10.0 and 3.5 months, respectively. There were no RECIST responses in any patient. The majority of toxicities were grade I and II. CONCLUSIONS: We demonstrated the feasibility and ability of Pre-Immature Dentritic Cells pulsed with HPV16 E6 (18–26) or HPV16 E7 (12–20) to induce a specific immune response against the relevant peptide despite the advanced disease of the cervical cancer patients treated on this trial. We believe that this observation deserves further investigations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-014-0353-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-42690782014-12-18 Pre-immature dendritic cells (PIDC) pulsed with HPV16 E6 or E7 peptide are capable of eliciting specific immune response in patients with advanced cervical cancer Rahma, Osama E Herrin, Vincent E Ibrahim, Rami A Toubaji, Anton Bernstein, Sarah Dakheel, Omar Steinberg, Seth M Eid, Rasha Abu Mkrtichyan, Mikayel Berzofsky, Jay A Khleif, Samir N J Transl Med Research BACKGROUND: The protein products of the early genes E6 and E7 in high-risk HPV types 16 and 18 have been implicated in the oncogenic capability of these viruses. Therefore, these peptides represent attractive vaccine therapy targets. METHODS: Thirty-two patients with advanced cervical cancer (HPV16 or 18 positive) were treated with HPV16 E6 (18–26) (Arm A) or HPV16 E7 (12–20) peptide (Arm B) pulsed on PBMCs in order to illicit immune response against the relevant peptide on both arms. These PBMCs were cultured for a short time (48 hours only) and in the presence of GM- CSF, accordingly, they were identified as “Pre-Immature Dentritic Cells”. RESULTS: 51Cr release assay and ELISPOT demonstrated evidence of specific immune response against the relevant peptide in 10/16 (63%) evaluable patients in arm A and 7/12 (58%) in arm B. HPV16 E6 was found to be homologous to HPV18 E6 in both vivo and vitro. The median overall survival (OS) and progression free survival (PFS) for the full cohort was 10.0 and 3.5 months, respectively. There were no RECIST responses in any patient. The majority of toxicities were grade I and II. CONCLUSIONS: We demonstrated the feasibility and ability of Pre-Immature Dentritic Cells pulsed with HPV16 E6 (18–26) or HPV16 E7 (12–20) to induce a specific immune response against the relevant peptide despite the advanced disease of the cervical cancer patients treated on this trial. We believe that this observation deserves further investigations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-014-0353-4) contains supplementary material, which is available to authorized users. BioMed Central 2014-12-16 /pmc/articles/PMC4269078/ /pubmed/25510844 http://dx.doi.org/10.1186/s12967-014-0353-4 Text en © Rahma et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Rahma, Osama E
Herrin, Vincent E
Ibrahim, Rami A
Toubaji, Anton
Bernstein, Sarah
Dakheel, Omar
Steinberg, Seth M
Eid, Rasha Abu
Mkrtichyan, Mikayel
Berzofsky, Jay A
Khleif, Samir N
Pre-immature dendritic cells (PIDC) pulsed with HPV16 E6 or E7 peptide are capable of eliciting specific immune response in patients with advanced cervical cancer
title Pre-immature dendritic cells (PIDC) pulsed with HPV16 E6 or E7 peptide are capable of eliciting specific immune response in patients with advanced cervical cancer
title_full Pre-immature dendritic cells (PIDC) pulsed with HPV16 E6 or E7 peptide are capable of eliciting specific immune response in patients with advanced cervical cancer
title_fullStr Pre-immature dendritic cells (PIDC) pulsed with HPV16 E6 or E7 peptide are capable of eliciting specific immune response in patients with advanced cervical cancer
title_full_unstemmed Pre-immature dendritic cells (PIDC) pulsed with HPV16 E6 or E7 peptide are capable of eliciting specific immune response in patients with advanced cervical cancer
title_short Pre-immature dendritic cells (PIDC) pulsed with HPV16 E6 or E7 peptide are capable of eliciting specific immune response in patients with advanced cervical cancer
title_sort pre-immature dendritic cells (pidc) pulsed with hpv16 e6 or e7 peptide are capable of eliciting specific immune response in patients with advanced cervical cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269078/
https://www.ncbi.nlm.nih.gov/pubmed/25510844
http://dx.doi.org/10.1186/s12967-014-0353-4
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